Synthesis, Conformations and Inclusion Properties of Hexahomotrioxacalix[3]arene Triamide Derivatives having Hydrogen-bonding Groups

The lower rim functionalizedhexahomotrioxacalix[3]arene triamide derivatives4a and 4b were synthesized from triol 1by a stepwise reaction. Extraction data for alkalimetal ions, transition metal ions, and alkyl ammoniumions from water into dichloromethane are discussed.Due to the strong intramolecular hydrogen bondingbetween the neighboring NH and CO groups, theiraffinities to metal cations were weakened.cone-4a shows a single selectivity ton-BuNH₃ ^plus while partial-cone-4aalmost has no affinity to cations. The anioncomplexation of cone-4a was studied by¹H NMR titration experiments. cone-4abinds halides through the intermolecular hydrogenbonding among the NH hydrogens of amide in a 1 : 1fashion in CDCl₃. The association constantscalculated from these changes in chemical shifts ofthe amide protons are K_a = 8520 M^-1for Cl^-1 and K_a = 1720 M^-1 forBr^-1. cone-4a shows a preference forCl^-1 complexation over Br^- complexation. Incontrast, cone-4b has good selectivity andaffinity to Ag^plus cation. A good Job plot proves1:1 coordination of cone-4b withAg^plus cation. The complexation mode of cone-4a with n-BuNH₃Cl and cone-4b with AgSO₃CF₃ were also demonstrated by ¹H NMR titration in CDCl₃.     

Synthesis of Methylene-Bridged Resorcin[4]arene Dimers

Methylene-bridged resorcin[4]arene dimers were synthesized by the Sc(OTf)₃-catalyzed hydroxymethylation of partially acetylated resorcin[4]arenes, and their preliminary complexation properties with tetraethylammonium ion were examined in CD₃OD by ¹H NMR spectroscopy. The dimers adopted a closed capsular conformation in this solvent and bound the guest molecule into their cavity.     

Synthesis and Molecular Recognition of Water‐Soluble S6‐Corona[3]arene[3]pyridazines

We report the efficient and scalable synthesis and molecular‐recognition properties of novel and water‐soluble S₆‐corona[3]arene[3]pyridazines. The synthesis comprises a one‐pot nucleophilic aromatic substitution reaction between diesters of 2,5‐dimercaptoterephthalate and 3,6‐dichlorotetrazine followed by the inverse electron‐demand Diels–Alder reaction of the tetrazine moieties with an enamine and exhaustive saponification of esters. The resulting S₆‐corona[3]arene[3]pyridazines, which adopt a 1,3,5‐alternate conformation in the crystalline state, are able to selectively form stable 1:1 complexes with dicationic guest species in water with association constants ranging from (1.10±0.06)×10³ M ^?1 to (1.18±0.06)×10⁵ M ^?1. The easy availability, large cavity size, strong and selective binding power render the water‐soluble S₆‐corona[3]arene[3]pyridazines useful macrocyclic hosts in various disciplines of supramolecular chemistry.     

Synthesis and Binding of Mannose-Specific Synthetic Carbohydrate Receptors

Synthetic carbohydrate receptors (SCRs) that selectively recognize cell-surface glycans could be used for detection, drug delivery, or as therapeutics. Here we report the synthesis of seven new C_2h symmetric tetrapodal SCRs. The structures of these SCRs possess a conserved biaryl core, and they vary in the four heterocyclic binding groups that are linked to the biaryl core via secondary amines. Supramolecular association between these SCRs and five biologically relevant C¹-O-octyloxy glycans, α/β-glucoside ( α/β-Glc ), α/β-mannoside ( α/β-Man ), and β-galactoside ( β-Gal ), was studied by mass spectrometry, ¹H NMR titrations, and molecular modeling. These studies revealed that selectivity can be achieved in these tetrapodal SCRs by varying the heterocyclic binding group. We found that SCR017 (3-pyrrole), SCR021 (3-pyridine), and SCR022 (2-phenol) bind only to β-Glc. SCR019 (3-indole) binds only to β-Man. SCR020 (2-pyridine) binds β-Man and α-Man with a preference to the latter. SCR018 (2-indole) binds α-Man and β-Gal with a preference to the former. The glycan guests bound within their SCR hosts in one of three supramolecular geometries: center-parallel, center-perpendicular, and off-center. Many host–guest combinations formed higher stoichiometry complexes, 2:1 glycan⋅SCR or 1:2 glycan⋅SCR , where the former are driven by positive allosteric cooperativity induced by glycan–glycan contacts.     

Synthesis,Structure, and Properties of O6‐Corona[3]arene[3]tetrazines

O₆‐Corona[3]arene[3]tetraazines, a new class of macrocyclic compounds, were synthesized efficiently in a one‐pot reaction from the nucleophilic aromatic substitution reaction between 1,4‐dihydroxybenzene derivatives and 3,6‐dichlorotetrazine in warm acetonitrile. In the crystalline structure, the resulting macrocycles adopt highly symmetric structures of a regular hexagonal cavity with all bridging oxygen atoms and tetrazine rings located on the same plane with phenylene units orthogonally orientated. The constitutional aromatic rings are able to rotate around the macrocyclic annulus, depending on the steric effect of the substituents and temperature, in solution. The electron‐deficient nature revealed by cyclic voltammetry, differential pulse voltammetry, and characteristic absorbances at a visible region show the O₆‐corona[3]arene[3]tetrazines to be suitable macrocyclic receptors for electron‐rich guests.     

Conformational features and recognition properties of a conformationally blocked calix[7]arene derivative

The shaping of a calix[7]arene macrocycle into cone-like structure 3, through exhaustive alkylation of doubly bridged calix[7]arene derivative 2 with bulky groups, has been investigated. Conformational details about the structure adopted by calix[7]arene derivative 3 in solution have been obtained by using chemical shift surface maps, as previously reported by our group. Thus, chemical shift contour plots indicated that 3 adopted a cone-shaped structure in solution analogous to that adopted by the known p-tert-butylcalix[7]arene heptacarboxylic acid derivative 4. Interestingly, the X-ray structure of derivative 3 showed a high degree of similarity to the theoretical structure, which confirmed the validity of the contour plots method. The preorganized calix[7]arene host 3 showed interesting recognition abilities toward both organic and alkali cations. In fact, an unprecedented endo-cavity complexation of linear and branched alkyl ammonium cations with a larger calix[7]arene host was evidenced. A comparable affinity for branched tBuNH(3)(+) and linear nBuNH(3)(+) guests was observed.     

A Water-Soluble Leggero Pillar[5]arene

The study of aqueous-phase molecular recognition of artificial receptors is one of the frontiers in supramolecular chemistry since most biochemical processes and reactions take place in an aqueous medium and heavily rely on it. In this work, a water-soluble version of leggero pillar[5]arene bearing eight positively charged pyridinium moieties (CWP[5]L) was designed and synthesized, which exhibited good binding affinities with certain aliphatic sulfonate species in aqueous solutions. Significantly, control experiments demonstrate that the guest binding performance of CWP[5]L is superior to its counterpart water-soluble macrocyclic receptor in traditional pillararenes.     

Alkyl Ammonium Ion Selectivity of Hexahomotrioxacalix[3]arene Triamide Derivative having the Intramolecular Hydrogen-Bonding Group

The lower rim functionalized hexahomotrioxacalix[3]arene triamide 4 with cone-conformation was synthesized from triol 1 by a stepwise reaction. The different extractability for alkali metal ions, transition metal ions, and alkyl ammonium ions from water into dichloromethane is discussed. Due to the strong intramolecular hydrogen bonding between the neighboring NH and CO groups in triamide 4, its affinity to metal cations was weakened. Triamide 4 shows a single selectivity to n-BuNH₃⁺. The anion complexation of triamide 4 was also studied by ¹H NMR titration experiments. Triamide 4 binds halides through the intermolecular hydrogen bonding among the NH hydrogens of amide in a 1:1 fashion in CDCl₃. The association constants calculated from these changes in chemical shifts of the amide protons are K_a = 223 M⁻¹ for Cl⁻ and K_a = 71.7 M⁻¹ for Br⁻. Triamide 4 shows a preference for Cl⁻ complexation than Br⁻ complexation.     

An Operative Electrostatic Slipping Mechanism along Macrocycle Flexibility Accelerates Guest Sliding during pseudo-Rotaxane Formation

A pseudo-rotaxane is a host−guest complex composed of a linear molecule encircled by a macrocyclic ring. These complexes can be assembled by sliding the host over the guest terminal groups. If there is a close match between the molecular volume of the flanking groups on the guest and the cavity size of the macrocycle, the slipping might occur slowly or even become completely hindered. We have previously shown that it is possible to overcome the restraints imposed by steric effects on the sliding process by integrating electrostatic attractive interactions during the slipping step. In this work, we extend our electrostatically assisted slipping approach (EASA) to a new host−guest system featuring a flexible macrocyclic ring and a series of asymmetric guests containing a cyclic tertiary ammonium group. Compelling evidence for pseudo-rotaxane formation is presented, along with thermodynamic and kinetic data. Experimental results suggests that the higher conformational flexibility of 24-crown-8 significantly increases the sliding rate, compared with the more rigid dibenzo-24-crown-8, without affecting complex stability. Furthermore, by combining the EASA and macrocycle flexibility, we were capable to slip a large eight-membered cyclic group across the 24-crown-8 annulus, setting a new limit on the ring molecular size that can pass through a 24-membered crown ether.     

Guest-Selective Recognition in a Flexible Bipyridinium-Based Framework in a Reversible Crystal-to-Crystal Fashion

A flexible bipyridinium-linker-based porous host framework with electron-accepting pore surface, namely, [Zn₂( L )(pmc)_1.5] ⋅ 12 H₂O ( 1 ; L⋅ Cl₂=1,1′-[1,4-phenylene-bis(methylene)]bis(4,4′-bipyridinium) dichloride, H₄pmc=pyromellitic acid) exhibits recognition of phenol and aromatic amine guests based on adsorbent–adsorbate charge-transfer interactions. Significantly, the resultant guest-encapsulated complexes 1@Guests can all be characterized by single-crystal X-ray diffraction. The host framework undergoes a reversible single crystal-to-single crystal transformation in response to the inclusion of different guests with flexible torsional motions of the hexagonal ring and the trapezoid-shaped bipyridinium groups. Such recognition can be visibly monitored and detected by obvious color changes. The host framework could also be recovered, and this suggested that guest sorption/desorption is reversible and that the host framework could be reused in potential applications. This work may provide an effective way to develop porous materials with special emphasis on applications involving guest recognition.     

Cucurbit[7]uril: A High‐Affinity Host for Encapsulation of Amino Saccharides and Supramolecular Stabilization of Their α‐Anomers in Water

Cucurbit[7]uril (CB[7]), an uncharged and water‐soluble macrocyclic host, binds protonated amino saccharides (D ‐glucosamine, D ‐galactosamine, D ‐mannosamine and 6‐amino‐6‐deoxy‐D ‐glucose) with excellent affinity (K_a=10³ to 10⁴ M ^?1). The host–guest complexation was confirmed by NMR spectroscopy, isothermal titration calorimetry (ITC), and MALDI‐TOF mass spectral analyses. NMR analyses revealed that the amino saccharides, except D ‐mannosamine, are bound as α‐anomers within the CB[7] cavity. ITC analyses reveal that CB[7] has excellent affinity for binding amino saccharides in water. The maximum affinity was observed for D ‐galactosamine hydrochloride (K_a=1.6×10⁴ M ^?1). Such a strong affinity for any saccharide in water using a synthetic receptor is unprecedented, as is the supramolecular stabilization of an α‐anomer by the host.     

Molecular Recognition Properties of Biphen[4]arene

Biphen[n]arenes (n=3, 4) are a new family of macrocyclic hosts. Here, we describe the molecular recognition behavior of hydroxylated biphen[4]arene (OHBP4) for the first time. A series of cationic guests with different sizes and shapes, including quaternary ammonium salts ( 1? PF₆ and 2? PF₆), pyridinium‐based guests ( 3? 2 PF₆– 6? 2 PF₆), and cobaltocenium hexafluorophosphate ( 7? PF₆), were chosen as model guest molecules. OHBP4 exhibits good selectivity towards the 2,7‐dibutyldiazapyrenium bis(hexafluorophosphate) ( 4? 2 PF₆) axle to form a [2]pseudorotaxane‐type complex. In contrast, hydroxylated biphen[3]arene (OHBP3) cannot bind with this big guest. In addition, OHBP4 strongly interacts with adamantane derivative 2? PF₆ and cobaltocenium 7? PF₆, which have tridimensional shape and relatively large size. The association constant of the 7 ⁺?OHBP4 complex in 1:1 (v/v) [D₆]acetone/CD₂Cl₂ solution is up to 3100±300 m ^?1.     

Highly Selective Binding and Inhibition of Pyr-His-Pro-NH2 (TRH) Function using a Polypyridinyl Macrocyclic Receptor with an Amphiphilic Cavity

Macrocycle, cyclo[4] [(1,3-(4,6)-dimethylbezene)[4](2,6-(3,5)-dimethylpyridine ( B4P4 ), shows highly selective binding affinity with protirelin (Pyr-His-Pro-NH₂; TRH) among the tested 26 drug or drug adductive substrates. The stable complexation in a 1:1 manner was fully characterized in solution, gas phase, and solid state study. Furthermore, B4P4 acts as an efficient TRH inhibitor even at [macrocycle]:[drug] <1:300, both in membrane transport and cellar incubation. The current work provides an unprecedented strategy for macrocycles to be efficiently used in drug target therapy.     

Pyridinium encapsulation within a novel cyano-footed pyrogallol[4]arene nanocapsule

A novel polar solvent-soluble tetra-functionalised cyano-footed calixarene forms a dimeric capsule, sealed via a hydrogen-bonding network between the two macrocycles, a single water molecule and a chloride anion, resulting in the encapsulation of a pyridinium guest, as shown in both solution and the solid state.     

Tetraphenylethene-Embedded Pillar[5]arene and [15]Paracyclophane: Distorted Cavities and Host–Guest Binding Properties

Two aggregation-induced emission (AIE) macrocycles (DMP[5]-TPE and PCP[5]-TPE) were prepared by embedding Tetraphenylethene (TPE) unit into the skeletons of Dimethoxypillar[5]arene (DMP[5]) and [15]Paracyclophane ([15]PCP) at meso position, respectively. In crystal, the PCP[5]-TPE showed a distorted cavity, and the incubation of hexane inside the DMP[5]-TPE cavity caused a distinct change in the molecular conformation compared to PCP[5]-TPE. There was no complexation between PCP[5]-TPE and 1,4-dicyanobutane (DCB). UV absorption experiments showed the distorted cavity of DMP[5]-TPE hindered association with DCB.     

Simulations of p-tert-butylcalix[4]arene with multiple occupancies of small guest molecules

Classical molecular dynamics simulations were used to study low-density beta(0)-phase p-tert-butylcalix[4]arene inclusion compounds with multiple calix occupancies of xenon, carbon dioxide, methane, and hydrogen guest molecules with guest-host ratios ranging from 1:4 to 4:1. Custom parameterized force fields were used for the guests and the AMBER force field for the calixarene units was validated in our previous work (Chem. Eur. J. 2006, 12, 5231). The inclusion energy and unit cell volume of the calixarene inclusion compound were determined for various guest occupancies and for occupancies greater than 1:1, strong guest-guest interaction effects are observed. The structure and energetics of the 2:1 CO(2)/beta(0)-phase inclusion compound were compared to those of the low-temperature 2:1 CO(2)/calixarene in which the guest molecules occupy both cage and interstitial sites.